Pulmonary ventilation and perfusion typically vary when pulmonary diseases are involved. (Nakagawa T, et al., J Magnetic Resonance Imaging 2001; 14:419-424). However, in current practice of thoracic cancer radiotherapy, the differences in pulmonary ventilation and perfusion are not considered when generating treatment plans. Lung volumes are deemed equal when placing radiation beams in planning. Clinicians and researchers have proposed to include normal lung sparing in thoracic cancer radiotherapy by introducing ventilation or perfusion imaging into radiotherapy treatment planning. (Lavrenkov K, et al., Radiother Oncol 2007; 83:156-162; Shioyama Y, et al.,Int J Radiat Oncol Biol Phys 2007; 68:1349-1358). If clinically implemented, introducing ventilation or perfusion imaging into radiotherapy treatment planning may reduce radiation toxicity to the lungs while still providing adequate radiation dose coverage to the tumors.
Different imaging modalities are currently used clinically for pulmonary ventilation evaluation. Nuclear medicine, including nuclear scintigraphy (Bunow B, et al., J Nucl Med 1979; 20:703-710; Gottschalk A, et al., J Nucl Med 1993; 34:1119-1126), single photon emission computed tomography (SPECT) (Harris B, et al., Am J Resp Crit Care Med 2007; 175:1173-1180; Petersson J, et al., J Appl Phisiol 2004; 96:1127-1136), and positron emission tomography (PET) (Melo M, et al., J Nucl Med 2003; 44:1982-1991; Willey-Courand D B, et al., J Appl Phisiol 2002; 93:1115-1122), is the most commonly used modality. Magnetic resonance imaging (MRI) (Levin D L, et al., Magn Reson Med 2001; 46:166-171; Suga K. et al., Am J Respir Crit Care Med 2003; 167:1704-1710) and computed tomography (CT) (Marcucci C, et al., J Appl Phisiol 2001; 90:421-430; Simon B A., J Clin Monitoring Computing 2000; 16:433-442) are also capable of pulmonary functional imaging.
The intrinsic spatial resolution of the gamma cameras used in scintigraphy and SPECT is determined by the quantum detection efficiency, the thickness of the NaI(Tl) crystal, the size of photomultiplier tube (PMT), the size of the collimator holes, the thickness of the collimator, and the energy of the incident photons. The typical intrinsic spatial resolution for modern scintillation cameras with crystals of ⅜ inch thickness is about 4 mm using with 99mTc radionuclide.
The spatial resolution of modem PET can be better than 5 mm in the center of the detector ring. Off-center spatial resolution is slightly worse. The factors that primarily affect the spatial resolution include (1) the intrinsic spatial resolution of the detectors which is mainly determined by the size of the individual scintillation crystal; and (2) the distance that the emitted positrons travel before annihilation, which is determined by the maximum positron energy of the radionuclide and the density of the tissue. The intrinsic spatial resolution of the detectors is the major limit of the spatial resolution of a PET system.
The higher spatial resolution is the advantage of MRI and CT over nuclear medicine. There are many techniques in MRI ventilation studies. The most common approach of MRI based pulmonary ventilation assessment uses gadolinium-based contrast agents. Due to the complexity of MRI based ventilation imaging, the clinical application of this technique is not common. Traditionally, iodine-based radiocontrast agents are used in CT based ventilation imaging.
Recently, Guerrero, et al. (Guerrero T, et al., Phys Med Biol 2006; 51:777-791; Guerrero T, et al., Int J Radiat Oncol Biol Phys 2005; 62:630-634) reported a method of ventilation imaging using 4-D CT, using no radiocontrast agents. The Hounsfield unit (HU) change was involved in the ventilation calculation. Deformable image registration was applied between respiratory phases of 4-D CT images. The deformation matrices calculated from the registration were used to link voxels in one phase and the corresponding voxels in the other phase. The HU differences between the corresponding voxels of the two phases were used in the ventilation calculation.
The advantages of ventilation imaging using 4-D CT data include: (1) 4-D CT is a mature technology and is commercially available; (2) no additional procedure such as contrast inhalation is needed, which makes the clinical implementation straightforward; (3) high spatial resolution of lung functional imaging can be achieved, which is a major advantage over nuclear medicine; (4) 4-D CT is a much less expensive procedure than other imaging modalities (it would be a great cost relief for clinical ventilation imaging); and (5) since 4-D CT is become routine for thoracic cancer radiation therapy planning, no additional procedure, such as a nuclear medicine or MRI imaging session, is needed for ventilation imaging. This reduces the cost and time for the radiotherapy patient.
The problem related to the HU change method is that the fluctuation of the HU in a CT image makes the ventilation image noisy and affects the HU-based ventilation images directly. The other problem with this method is the edge artifact. The mismatched regions on the low-high density interface, such as the interface between the lung tissues and blood vessels, and between the lung and chest wall, cause artifact of high ventilation spikes. This is because the voxel-to-voxel ratio of the intensity is used in the ventilation images, which magnifies the noise in CT images. Usually, a number of voxels are averaged for ventilation calculation using this method to smoothen the noise. This would make the spatial resolution of ventilation images coarser, losing the advantage of CT images over nuclear medicine ventilation images. The partial volume effect in CT images makes the CT voxel intensity higher or lower, which in turn creates artifact in the ventilation images.
Any voxel-to-voxel mismatch at the edge of high-low intensity interface, such as blood vessels and lung tissue interface, chest wall and lung interface, would cause spikes in ventilation images. The mismatched edges can be seen in FIG. 6. Even with averaging technique, these spikes would still introduce false high ventilation volumes.